B6.129-Htt^tm5Mem/J

Stock number: 003598
Product name: Hdh^Q111
Strain synonyms: HdhQ111 KI
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

These Hdh^Q111 knock-in mice exhibit Huntington's-like pathology. As of 2023, The Jackson Laboratory Repository Stock No. 003598 will use breeders with CAG repeat expansion range of ~103-117 [as determined by Laragen assay] and distribute mice with CAG repeat expansion range of ~101-121 [as determined by Laragen assay].

Detailed description

As of 2023, The Jackson Laboratory Repository Stock No. 003598 will use breeders with CAG repeat expansion range of ~103-117 [as determined by Laragen assay] and distribute mice with CAG repeat expansion range of ~101-121 [as determined by Laragen assay].

Hdh^Q111 was created with 111 CAG repeat units in the first exon of the endogenous Htt gene. Huntington's-like pathology is seen in the striatum, including nuclear localization of the protein, N-terminal inclusions, and insoluble aggregate formation.

Instability of the length of the CAG repeat between generations is seen. As such, the CAG repeat expansion size should be monitored in breeders at every generation. If labs do not have access to the appropriate equipment for determining CAG repeat length, CAG repeats can be evaluated on a fee-for-service basis by Laragen, Inc.

Expression of the Htt^tm5 phenotype occurs earlier than in Htt^tm4 (Stock No. 003455).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes and 111 CAG repeat units was used to disrupt exon 1. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric male animals were crossed to CD1 mice, and then backcrossed to C57BL/6J for 6 generations.

Allele

Symbol: Htt^tm5Mem
Name: targeted mutation 5, Marcy E MacDonald
MGI accession ID: MGI:1861935
Generation method: Targeted
Attributes: Humanized sequence
Synonyms: Hdh^Q111
Marker symbol: Htt
Marker name: huntingtin
Marker synonyms: C430023I11Rik; Hd; Hdh; htt; IT15; LOMARS
Chromosome: 5
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: This allele carries 109 CAG repeat units, with 111 glutamines, in the first exon of the endogenous gene. It is a derivative of Htt^tm8 in which the neo cassette has been removed via cre-mediated recombination.